To successfully pursue biomedical research into the mechanisms of immune mediated lung injury, one must have a solid understanding of modern techniques in molecular biology, immunolgy, and pulmonary physiology. My training in pulmonary medicine has given me the opportunity to extensively study pulmonary physiology while diagnosing and treating patients with a variety of lung diseases. While I have begun to acquire some skills in molecular biology, an extended period of continued mentored training is critical for the development of the experience and skills necessary to pursue high quality research into lung disease. Dr. Koller's expertise in the generation and characterization of mouse models to study the pathogenesis of disease makes her laboratory an ideal environment for this mentored training. The overall objective of this project is to determine the contribution of adenosine to allergic airways disease by utilizing mouse models in which the expression of the A2b and A3 adenosine receptor genes have been inactivated using homologous recombination in embryonic stem cells. Specifically, we will define the expression of these receptors on immune cells and in murine lung, determine the receptor responsible for adenosine-induced mast cell degranulation, and determine the significance of activation of these receptors by adenosine to the overall pathogenesis of allergic airways disease. This project will provide extensive hands-on training in state of the art molecular biology, immunology, and murine pulmonary physiology in an environment that will promote the development of independent research skills necessary for a career investigating the mechanisms of pulmonary disease.